Eyelid Margin Wipes Comprising Chemical Means for Temperature Adjustment

ABSTRACT

An eyelid margin wipe comprising chemical means for adjusting the temperature of the wipe relative to the ambient temperature. The wipe is particularly useful for treatment of disorders of the eyelid or eyelid margin such as meibomian gland dysfunction.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application is a continuation of application Ser. No. 13/932,426,filed on Jul. 1, 2013, which is a divisional of application Ser. No.11/120,757, filed on May 3, 2005, now U.S. Pat. No. 8,506,539, which isa continuation, under 35 U.S.C. §120, of International PatentApplication No. PCT/GB2003/004782, filed on Nov. 5, 2003 under thePatent Cooperation Treaty (PCT), which was published by theInternational Bureau in English on May 21, 2004, which designates theUnited States and which claims the benefit of Great Britain PatentApplication No. GB 0225795.4, filed Nov. 5, 2002. All above-referencedprior applications are incorporated by reference herein in theirentirety and are hereby made a portion of this specification.

FIELD OF THE INVENTION

The present invention relates to wipes. More particularly, it relates toeyelid margin wipes. In a further aspect, the present invention relatesto a method of treatment of disorders of the eyelid margin such as thosecaused by meibomian gland dysfunction.

BACKGROUND OF THE INVENTION

Meibomian glands, which are positioned throughout the eyelid margins,provide lipid like secretions (known as meibum) to the surface of theeye. When blinking occurs, the upper eyelid moves downwardly over theeye and assists the lipid secretion between the margins of the eyelids.Upon eye opening, the upper lid moves upwardly and pulls a sheet oflipid upwardly to form a film over the eye. This lipid sheet coats theaqueous part of the tear layer which in turn coats the surface of theeye. The presence of this lipid sheet restricts evaporation of the tearlayer such that the surface of the eye is maintained in a moistenvironment. Failure of the meibomian glands will mean that the requiredlipid layer is not properly formed and evaporation of the tear layerwill occur rapidly which will lead to sensations of dryness, irritationand burning.

The main cause of failure of the meibomian glands is due to theirbecoming clogged. A number of factors may lead to clogging. For example,hormonal changes, particularly in levels of oestrogen, can result inthickening of the oils which will in turn clog the glands. In addition,it has been suggested that changes in oestrogen levels may causestaphylococcal bacteria, which naturally inhabit the eye, toproliferate. Unfortunately, this proliferation may cause the bacteria toinvade the meibomian glands which can cause a decrease in the secretionof lipids from the glands.

Additionally or alternatively the clogging may be caused byimmunological factors such as sebhorreic blepharitis or systemicdiseases such as acne rosacae. Blepharitis also affects the lid marginand is often associated with meibomian gland dysfunction. Blepharitisoccurs in increasing prevalence with the age of the patient. Whereblepharitis occurs, inflammation of the lid margins may be noted oftenin combination with redness. In addition, scales, crusts and/or marginalulcers may be observed.

Mechanical failure may also cause the glands to dysfunction. Furtherinformation relating to the aetiology of meibomian gland dysfunction maybe found in Gutgessel V J et al (1982) Histopathology of Meibomian GlandDysfunction. Ma. J. Opthal 94: 383-388.

An increased disfunction of the meibomian gland is noted with age and inaddition may be seen to be higher in contact lens wearers. In Ong B Land Lark J R (1990) Meibomian Gland Dysfunction: Some Chemical,Biochemical and Physical Observations, Opthal: Physiol Opt 10: 144-148 a30% prevalence of gland dysfunction was noted in contact lens wearersand 23% in non-contact lens wearers in a preliminary study involving 140subjects, half of which were contact lens wearers.

In Ong B L (1996) “Relation Between Contact Lens Wear and MeibomianGland Dysfunction” Optom & Vis Sci 73: 208-210, 231 subjects wereevaluation of which 81 were contact lens wearers. A prevalence tomeibomian gland dysfunction was noted in 43% of the contact lens wearersand 35% of the non-contact lens wearers.

The effect of age was considered by Horn M M et al in “Prevalence ofMeibomian Gland Dysfunction 1990 Optom & Vis Sci 67: 710-712. Here 298patients aged from 10 to over 60 were tested. The results reported anoverall prevalence to dysfunction of 39%. However, the levels were lowat a young age with a marked increase being noted as age increased. Foreach decade up to 49 years there was an increase with the maximum beingat 40%. From 50 to 59 years a prevalence of 51% was noted, and forpatients over 60, the prevalence was noted to have risen to greater than67%.

In addition to contact lens wearing and aging, abnormal behaviour of themeibomian glands may be exacerbated by illness or the use of cosmetics.

The severity of meibomian gland dysfunction is variable and depends onthe stages of the dysfunction. In the initial stages increased secretionis noted. This leads to over development of the epithelial cells liningthe duct of the glands and to modification of the lipid composition.These cells may be excreted from the glands producing dandruff-likescales.

In the intermediate stage, the change in lipid composition leads to anincrease in the melting point of the lipid, such that it becomes a pastelike solid at eyelid temperature which leads to partial or totalblockage of the meibomian glands. The further production andaccumulation of desquamated epithelial cells adds to the blockage of thegland orifices.

In the advanced stages, long term blockage of the glands can lead to themeibomian glands becoming atrophied. It is essential to commencetreatment before the final stage is reached since once the glands havebecome atrophic, the dysfunction is irreversible.

The slow evolutionary nature of the dysfunction means that the stages ofmeibomian gland dysfunction is often different for different glandsalong the same eyelid margin.

Conventionally, the blocked glands are treated with a cloth, faceclothor towel which is immersed in boiling water, allowed to partially cooland then placed over closed eyes. The aim of the treatment is to meltthe solidified lipids and to loosen the debris which has collectedaround the glands and at the base of the eyelashes. It is sometimessuggested that salt should be applied to the cloth.

Whilst this treatment may be effective if correctly performed, it doessuffer from certain disadvantages and drawbacks. The main drawback isthat the user must estimate when the cloth is at the correct temperaturebefore placing it over the eyes. If the cloth is too hot, there is arisk that the patient will be scalded. Conversely, if the cloth hascooled too much, the treatment will be ineffective. Further, it is acumbersome and awkward treatment which cannot readily be utilisedoutside of the home. Since the procedure is complex and time consumingit is often abandoned by the patient before the required benefits areobtained. A further disadvantage of this method is that even if thecloth is at the correct temperature at the start of the treatment, itwill rapidly cool such that the required temperature is only maintainedfor a short period of time.

An additional drawback is that there is a risk of bacterialcontamination as the cloth is not sterile. This is a particularlyserious problem for contact lens wearers.

A second stage of treatment is to treat the eyelid margin with cleaningagents. Examples of suitable cleaning agents are those sold under thetrade marks “Lid-Care” by CibaVision and “Supranettes” by Alcon.

Whilst the use of hot cloths and cleaning agents may go some way toaddressing the symptoms of meibomian gland dysfunction, there is still aneed for a treatment system which will overcome the above-mentioneddisadvantages and which can be readily used by patients with busylifestyles.

Other eye problems may benefit from treatment with a hot wipe or in somecircumstances with a cooled wipe. These problems include the eyesymptoms encountered by hayfever sufferers and the swelling/edema causedby trauma. The application of a cooled wipe to the eye region may alsobe beneficial in the treatment of headaches. It is recommended that, forexample for the treatment of swelling, cooling with cold water at about8° C. for about 30 minutes is recommended. Although for ice therapy theapplication time may be significantly shorter. Conventionally, where theextreme treatment in which ice is applied it is necessary to take extracare to ensure that ice is not applied directly to the skin sinceburning can occur.

SUMMARY OF THE INVENTION

It is therefore desirable to provide a treatment which provides the userwith control over the temperature and which is simple to operate.

Whilst various proposals have been made for heating bandages and thelike, such as those systems described in U.S. Pat. No. 5,662,624, WO98/29079, U.S. Pat. No. 6,465,709, WO 01/03619 and U.S. Pat. No.6,265,631 none provide the required level of control over thetemperature and maintenance of temperature. Further, they are notconfigured to be suitable for use in the delicate and sensitive eyearea.

Thus according to the first aspect of the present invention there isprovided an eyelid margin wipe comprising chemical means for adjustingthe temperature of the wipe relative to the ambient temperature.

It should be noted that in general the primary function of the wipe isto clean away one or more of: dead cells; debris; meibomian secretions;and the like. Whilst in some arrangements of the present inventionsecretions may be adsorbed onto the surface of the wipe, in general thewipe of the present invention would not be regarded as an absorbentarticle.

By “adjusting the temperature” we mean that the temperature of the wipewill change relative to ambient temperature to a pre-determinedtemperature. The change in temperature may be a heating or cooling ofthe wipe.

The temperature to which the wipe will be adjusted will be dependent onthe end-use to which it is to be put. However, it will be understoodthat by selection of the appropriate chemical means, the requiredtemperature to achieve the desired results can be reproducibly achievedwith each wipe thereby obviating the problems associated with the priorart where the cloth may not be adjusted to the correct temperature.

For the treatment of the symptoms of meibomian gland dysfunction, therequired temperature is that required to melt the set lipid. Asmeibomian secretion is usually a mixture of lipids there is normally nosharp melting point and the various lipids present may have meltingpoints over a wide temperature range. Ong B L and Larke J R in MeibomianGlad Dysfunction: Some Clinical, Biochemical & Physical Observations(Opthal. Physiol. Opt 1990, 10, April: 144-148) reported a range of from32° C. to 40° C. with a significant difference in melting points beingnoted between normal and abnormal lipid samples.

Other experiments have suggested different temperature ranges. Forexample, Tiffany J M & Marsden R G in The Influence of Composition OnPhysical Properties of Meibomian Secretion In The Preocular Tear Film inHealth, Disease and Contact Lens Wear (Dry Eye Institute, Lubbock Tx1986; 597-608) reported a range of from 19.5° C. to 32.9° C.

These differences are attributable to the make-up of the secretion. Thesecretion is generally fluid enough to flow from the glands and spreadto form a superficial tear film layer.

For the wipes of the present invention, in the circumstances in whichthe temperature adjustment is to be a rise in temperature for examplefor the treatment of meibomian gland dysfunction, temperatures in theregion of from about 40° C. to about 55° C. will generally be desirablewith temperatures in the region of from about 45° C. to about 52° C.being particularly preferred.

The adjusted temperature is preferably maintainable for at least about 5minutes, preferably about 8 minutes and most preferably about 10 or moreminutes.

For the wipes of the present invention, in the circumstances in whichthe temperature adjustment is to be a lowering in temperature forexample to treat swelling/edema following trauma temperatures in therange of from about 0° C. to about 25° C. are desirable withtemperatures in the range of about 5° C. to about 10° C. beingparticularly preferred. It is desirable that cooling can be maintainedfrom about 5 minutes to about 30 minutes.

To assist the user, the wipe may incorporate an indicator which confirmsto the user that the required temperature has been reached. Theindicator may be a temperature sensitive colour indicator which willchange colour from a first to a second colour when the requiredtemperature is achieved. In one arrangement the colour change will bereversible such that when the wipe is no longer at the desiredtemperature or has fallen outside the desired temperature range theindicator will revert to the first colour. The colour indicator may beprovided by any suitable means. In one arrangement at least a part ofthe wipe may be coated with a temperature reactive ink or treated with atemperature reactive dye. Thus the user will be advised to wait until aparticular colour is achieved before using the wipe and to cease useonce the particular colour disappears.

The wipe of the present invention may be of any suitable configuration.In one arrangement it may be a sheet-like material. In one alternativearrangement, the wipe may have increased thickness. The material may beimpregnated with or coated with the chemical temperature adjustingmeans.

The wipe may be a cloth-type material. Where the wipe is formed from acloth-type material, the cloth may be of any suitable material and maybe formed by any technique including weaving, air-laying and the like.Thus the material may be woven or non-woven. The cloth may be made fromnatural or synthetic fibres or a mixture of both. The material may beselected for its compatibility with the chemical means used foradjusting the temperature of the wipe. Additionally or alternatively,the material may be selected for more aesthetic considerations such assoftness and eye-appeal. The cloth may be of any suitable thickness.Suitable thicknesses include those from about 0.2 mm to about 5 mm, morepreferably from about 1 to about 4 mm. However, thicker arrangements maybe desirable in some circumstances.

In a second alternative material, the wipe, rather than being formed ofa cloth-type material, may be formed from a sponge-type material. Thesponge may be a natural or synthetic sponge. The sponge-type materialwipe may be of any suitable size and may have a thickness greater thanthat noted for the cloth-type material wipe.

In a third alternative arrangement, the wipe may be provided as amulti-layered material. The material in each layer may be the same ordifferent. For example, the wipe may comprise a sponge material havingattached to one or both surfaces thereof a cloth-type material. Wherethe cloth-type material is applied to two opposing faces of asponge-type material, the material used in each face may be the same ordifferent. The multi-layered wipe may be of any suitable thickness.

The wipe may comprise several layers of cloth-type material, each ofwhich may be different. Where a layered structure is used, thetemperature adjusting means may be located in or on one or more of thelayers.

Where the wipe is to be coated with one or more temperature adjustingmaterials, it may be coated on one or both sides of the wipe. However,the chemical means is preferably only applied to one side to allow anuncoated free side of the wipe. In some arrangements the uncoated sidemay be applied to the eye. In alternative arrangements, the uncoatedside may be used for application of materials such as therapeuticmaterials, cleaning fluids or the like.

Where the wipe is impregnated with temperature adjusting material, thematerial may be located throughout the wipe or, for example, may beprovided in such a manner that particles of the temperature adjustingmaterial will not come into contact with the eye when in use. Thetemperature adjusting material may be immobilised in a non-woven padwhich is provided, for example, as the cloth-type material or as onelayer in a multi-layered arrangement.

In a further alternative arrangement, or where required by thetemperature adjusting means selected, the wipe may be an arrangementcomprising a pocket or the like into which the temperature adjustingcomponents may be placed, either directly or in a separate container. Inan alternative arrangement the material from which the wipe is formedsurrounds the temperature adjusting means, for example is wrapped aroundthe temperature adjusting means which may be placed in a suitablecontainer.

The temperature adjusting component may be a self-heating or coolingdevice or a device relying on external sources of heat or cold. Whereexternal devices are used to cause the temperature adjusting means tochange temperature, these may be conventional sources such as ovens,microwave ovens, refrigerators and the like. In one alternativearrangement, the external device may be a purpose-built device. In onearrangement, the chemical temperature adjusting means may be activatedby a conducting foil-strip located in the wipe which may be connected toan energy source.

The wipe is preferably single use but in one alternative, althoughnot-preferred, arrangement, the wipe may be re-usable. Where multi-useis desirable, the wipe will generally be configured such that itcomprises a pocket for containing the temperature adjusting means whichis preferably located in a separate container. On re-use, thetemperature adjusting means container will generally be removed andreplaced with a fresh container. Where the wipe is to be re-used in thismanner, it is preferably produced from washable material.

The wipe may be of any suitable shape and/or configuration. Suitableshapes include squares, rectangles, circles and ovals. In onearrangement, the wipe may be finger-shaped. The wipe may be of anysuitable size. It may be sized to be approximately the size of one eyeregion or may be sized such that it could be used on two eyessimultaneously. In this latter arrangement, a band, such of elastic, maybe provided so that the user can wear the wipe for a period of time.

The wipe may be shaped to have a profile which assists its operation.For example, the wipe whether of a square, rectangular, circular orovoid shape may be curved such that when laid over the closed eye, itwill follow the curvature of the eye and ensure that the temperature isprovided across the entire eyelid and eyelid margin.

In one arrangement the wipe may be coated, at least on one surface, witha material, such as a polymeric material which is soft such that itmoulds to the shape of the users eye and thereby ensures that thetemperature is provided across the entire eyelid and eyelid margin. Inone arrangement the polymeric material may not be soft at roomtemperature but softens as the temperature of the wipe increases.

In one preferred arrangement the wipe may include a pocket into whichthe user may insert one or more fingers. This arrangement willfacilitate the user when performing any rubbing of the eyelid marginwhich may be desirable, for example as part of the treatment ofmeibomian gland dysfunction. In a most preferred arrangement, the wipemay be shaped to correspond to the shape of a finger. One benefit ofthis arrangement is that the user will be able to readily control thewipe during any rubbing motion.

In one alternative arrangement, the configuration of the wipe maycorrespond to two or more finger shapes, conjoined, for example by a webof material. In one arrangement, each fingered shaped portion would bearranged to receive at least part of one finger. In a preferredarrangement of the present invention one or more finger portions wouldinclude the heating means and one or more other finger portions would beof non-heated fabric which might be used for massaging or for theapplication of, for example, cleansing agent.

In one arrangement, the wipe, however configured, may include anadhesive portion so that it can be left in place on the eye to warm orcool the eye prior to massaging taking place. In one arrangement, theadhesive portion may comprise at least a part of one side of the wipe.In one alternative arrangement the whole of one side may be adhesive. Inthis arrangement, the user will normally turn the wipe over prior tomassaging/wiping such that massaging/wiping is carried out with anon-adhesive side of the wipe. Where an adhesive portion is used, thewipe will generally be provided with a removal strip, such as a polymerstrip or a paper strip surface treated with silicone, in place toprotect the adhesive material. Any suitable adhesive material may beused which enable the wipe to be held in place without causingirritation to the delicate eye area and which will enable the wipe to bereadily removed without causing discomfort to the user. Examples ofadhesive materials include acrylic adhesives, liquid absorbingadhesives, such as a hydrocolloidal or hydrogel adhesives, naturalrubber or synthetic rubber.

The adjustment in the temperature of the eyelid wipe may be achieved byany suitable means. However, the selection of the appropriate means willgenerally be dependent on the required temperature for the wipe and thesuitability of any chemical components for use in the delicate eyelidregion. The ability of the material to maintain the temperature for therequired period of time may also be a factor which will be taken intoconsideration when selecting the heat adjusting means. Where chemicalsare to be used which are not suitable for direct application to the skinor eyelid margin, the arrangement in which the heat adjusting means areplaced in a separate container within the wipe will generally beutilised, although any means for separating them from the skin may beused.

The method chosen to accomplish the adjustment in temperature preferablyenables the wipe to reach the desired temperature in a short period oftime, usually less than about 60 seconds. Times in the order of fromabout 30 to about 60 seconds are particularly preferred.

In one arrangement, the wipe, however configured, may alter intemperature on exposure to oxygen, generally the oxygen in the air.Examples include the use of wipes impregnated with, or coated with,material which on exposure to air oxidises and in doing so generatesheat. In one arrangement, the material which on exposure to air oxidisesto generate heat may be placed in an oxygen-permeable bag which may beenclosed within the wipe or placed in a pocket in the wipe.

Suitable materials include those which form an oxide when reacted withoxygen at room temperature including: iron, aluminium, magnesium,titanium, manganese, zinc, molybdenum and tin oxide (II) with ironpowder being particularly preferred. The material will generally beprovided in powder form to provide a large surface area on whichoxidation may occur. The material used may be a mixture of two or moreof the foregoing. Further examples of suitable materials include: metalsulphides, polysulphides or hydrosulphides mixed with a catalyst carriedon a carbonaceous material; powdered solids such as elemental iron,mixed with salts and water; mixtures of iron powder, water, cellulose,salt and vermiculite activated carbon; iron powder, water, salt andactivated charcoal; iron or other metals mixed with alkali metal saltsand a catalyst; redox systems such as metal powder (usually ferrous), ametal chloride, water and a water absorber; and alkaline earth metaloxides, such as magnesium oxide, with chlorides or sulfides of alkalimetals or alkaline earth metals. It will be understood that some of thecomponents of the mixtures listed do not directly contribute to the heatgenerating reaction but are present to modify or control the reaction.For example, catalysts, assistants, fillers and moisteners may bepresent.

Where the temperature adjustment means operates on exposure to air, thewipes will generally be provided to the user in an airtight package.Examples of airtight packages include plastic envelopes and foil,particularly aluminium foil, pouches. As the package is opened, the wipewill be exposed to air and the adjustment in temperature will commence.

In one alternative arrangement, the wipe, however configured, may alterin temperature on exposure to water. In this arrangement, materialimpregnated into, coated on, or enclosed within the wipe may be based onchemical substances which generate heat when in the presence of water.The heat generated may be, for example, heat of hydration, dissolutionor oxidation. The material which generates heat on contact with watermay be placed in a water-permeable bag which may be enclosed within thewipe or placed in a pocket in the wipe.

In use, these wipes would need to be treated with water, or an aqueoussolution in order for the heat to be generated. Suitable aqueoussolutions include saline, potassium salts, calcium salts, aluminiumchloride, calcium chloride, magnesium chloride, potassium sulphate,magnesium sulphate, sodium sulphate and the like. Other solutions mayalso be used to “wet” the wipe, including those solutions commonly usedin contact lens care regimes. The water or other solution may be appliedby immersing the wipes in the water or solution or the water/solutionmay be poured or sprayed onto the wipe.

Suitable materials for altering the temperature of the wipe whencontacted with water or other suitable solution include sodiumhydroxide, cobalt, chromium, iron, iron hydroxide, magnesium, manganese,molybdenum, tin oxide (II), titanium and calcium hydroxide. Thesepowdered solids may be used alone or in combination. Also suitable arepowdered solids such as iron. These may be used alone or with othercomponents such as salt and activated charcoal, or with alkali metalssalts and a catalyst. In addition, hydratable organic or inorganic saltssuch as calcium chloride, calcium sulfate, cerous chloride, sodiumcarbonate, aluminum chloride, magnesium chloride, magnesium sulfate,zinc citrate, zinc sulfate, zinc nitrates, alkali metal carbonates,alkali metal borates, alkali metal acetates, alkali metal citrates oralkali metal phosphonates may be used. Similarly mixtures such as:anhydrous calcium chloride, cerous chloride, cesium hydroxide, sodiumcarbonate and organic oxide or salts such as calcium oxide, aluminiumchloride or calcium nitrate; sodium chloride with an organic oxide orsalt; hypochlorite salts with cellulosic or cellulosic-containingmaterials; anhydrous calcium chloride and calcium oxide; anhydrouscalcium chloride, anhydrous sodium acetate and calcium oxide; boroncompounds having a boron-oxygen-boron bond; anhydrous glycol; silicagel; activated alumina; and synthetic zeolites may be used. Anhydrouszeolites, hydratable organic or inorganic salts, magnesium sulphate,magnesium chloride, calcium chloride and calcined gypsum areparticularly preferred. Each of these would produce an exothermicreaction when mixed with water.

Also suitable are ammonium nitrate, sodium nitrate, ammonium sulphurate,potassium nitrate, sodium thiosulphate, ammonium chloride, ammoniumbromide, ammonium iodide, potassium chloride and tin chloride dihydratewhich each produce an endothermic reaction when mixed with water.

Whichever method is used to alter the temperature, additional materialsmay be used to control or extend the reaction.

In a further alternative arrangement, the wipe may contain twocomponents which are kept separate until temperature adjustment isrequired at which time they are allowed to mix.

This technology may be provided by placing one of the components in afrangible container which may be enclosed within the wipe or, whereappropriate, the wipe may comprise a pocket for holding a containercomprising one of the components or a container comprising bothcomponents separated by any suitable means. In one alternativearrangement, a single container may be used which comprises two or morechambers, each containing one component. When required, the componentsmay be mixed, for example, by the breakage of a frangible sealseparating the two chambers such that a reaction between the twocomponents can occur. Where the reaction is an exothermic reaction,heating will occur. Similarly where the reaction is an endothermicreaction, cooling will be achieved.

The container may be made of any suitable material. Where the componentto be included in the container is water or an aqueous solution, thematerial from which the component is manufactured will bewater-impermeable. Any suitable water-impermeable material may be usedprovided that it has the sufficient level of brittleness to rupture whenpressure is applied. Suitable materials include polymers such aspolyethylene, polypropylene, polyvinyl acetate, polyurethane, siliconerubber and polyvinyl chloride.

The container may be constructed such that the contents can be deliveredto the other component in a pre-determined and controlled manner, suchthat the temperature change can be maintained for the desired period oftime. For example, the container may be a flexible container havingsealed orifices which open when pressure is applied to the container.The size of the orifices will determine the time period over which thecomponent will be released from the container.

In an alternative arrangement one of the components may be located onthe wipe or may be impregnated in the material of the wipe and the othercomponent may be located within a container which is frangible or whichhas a frangible seal, and which is located within the wipe or within apocket in the wipe.

In one example of a two component system, the first component may be acompound which generates heat on contact with water, such as calciumoxide, anhydrous magnesium sulphate, colloidal clay or any other of thecompounds identified as generating heat on contact with water above andthe second component, separated from the first, may be water, saline orother aqueous solution, including surfactant solutions. The secondcomponent may additionally include active agents such asanti-inflammatory or anti-bacterial agents.

Other two component systems include: magnesium/iron alloys andelectrolytes (suitable electrolytes include saline); magnesium chloridewith ethylene glycol; sodium thiosulfate with ethylene glycol;boron-compounds having a boron-oxygen-boron bond with a protic materialsuch as water, methanol, ethanol, propanol, isopropanol, butanol, loweramines, lower alkanol amine, aliphatic oxides and polyols.

In another example of a two component system, the first component may bea compound which cools down on contact with water such as sodium nitrateand the second component separated from the first until activation ofthe device may be saline, water or other aqueous solutions such assurfactants. The second component may additionally contain active agentssuch as anti-inflammatory or anti-bacterial agents.

A further example of a two component system is an oxido-reduction systemin which an oxidising agent and a reducing agent are used which undergoreaction when combined to generate heat. Examples of oxidising agentsinclude hydrogen peroxide, urea hydrogen peroxide, sodium peroxide,sodium perborate, sodium persulfate, ammonium persulfate and potassiumpersulfate. Examples of reducing agents include thiourea compounds suchas 1-phenyl-2-thio-barbituric acid. Preferred reactions include: ahydride such as an alkali metal or alkaline earth metal borohydride suchas sodium, potassium or calcium borohydrides with an aldehyde such asglyceraldelyde, a ketone such as acetone, a peroxide or a sulfoxide;thiooxypyrimidine or 2-thio-4 oxypyrimidine with hydrogen peroxide orsodium perborate; thiourea with hydrogen peroxide; or alkali metal saltsor manganese and chromium oxides such as potassium permanganate orpotassium chromate and alcohols or polyols such as glycerin.

A still further example of a two component system includes the reactionbetween an aqueous salt solution, such as aqueous sodium solution, andseed crystals or metallic triggers that, on contact with the aqueoussalt solution, will activate crystallisation and thereby generate heat.Examples include aqueous sodium acetate solution and sodium acetate seedcrystals. One benefit of using a system in which crystallisation occursis that the presence of the resultant crystals within the wipe may bebeneficial during massaging of the eye. Some reactions in a twocomponent such as magnesium sulphate and water, a first exothermicreaction will occur followed by a crystallisation which will alsogenerate heat thereby prolonging the heating of the wipe.

Whichever systems are used to adjust the temperature of the wipe,materials may be present to regulate the reaction that causes theadjustment of temperature. Suitable materials include gelling agents,polymers and the like.

It will be understood that some mixtures identified include materialswhich do not contribute to the heat adjusting reaction but are adjunctspresent to control the reaction. Similarly, materials may be present toextend the temperature adjusting reaction. For example, where the heatadjusting reaction is an exothermic reaction, water-containing materialthat will release water above a particular temperature may be present.

In addition, physical means may be included in the wipe to control thetemperature delivered to the user. For example, one or more insulatinglayers, may be included. Similarly one or more diffusing layers may beincorporated. In one alternative arrangement a covering may be appliedto the wipe which assists in the temperature control. The thickness ofthe one or more layers in the wipe may be selected to assist withtemperature control.

Thus, the wipe may include a reflective layer and/or a conductive layerto direct the heating or cooling towards one surface of the wipe. Thereflective layer and/or the conductive layer may be made of any suitablematerial. Examples of suitable materials include metal foils such asaluminium foil. Also suitable are amorphous metallic oxide layers whichare very thin and which may be translucent.

The layered wipe including for example diffusion layers, insulatinglayers and the like and the heat adjusting means located in a container,may have any suitable thickness but will generally be in excess of about5 mm.

It will be understood that whatever method of heat control is selected,by selection of particular chemical reactions, a required temperaturecan be achieved and controlled without any decisions having to be takenby the user. In addition the structure of the wipe can be selected tooptimise the temperature and control its application to the user.

A further advantage of the present invention is that the chemical meansmay be selected such that the required temperature can be maintained forsufficient time to allow effective treatment to be carried out.

Further, since the reaction will be reproducible in each wipe containingthe same temperature adjusting means, the user can be assured of theappropriate temperature to achieve efficacy at each treatment withoutthe risk of burning of the delicate skin in the eye region.

Whilst the present invention is described with particular reference tothe treatment of meibomian gland dysfunction, it will be understood,that dependent on the temperature of the wipe, there may be a variety ofuses. For example, a cooled wipe may be useful in the treatment of thesymptoms of, for example, hay fever. The wipes may also be useful in thelid care of contact lens wearers and the sufferers of dry eye and alsoin the removal of eye cosmetics. In this latter arrangement, in additionto the heat management means, the wipe may include solutionsparticularly suitable for the removal of eye make-up and/or having lipidsolubilising properties.

The eyelid wipe may be provided in a sealed pack formed from anysuitable material. Examples of suitable materials include plastics andmetal foils. The wipe is preferably sterile.

Where the temperature adjusting means is immobilised in the wipe ratherthan being placed in a container within the wipe or a pocket in the wipea binder may be used. Suitable binders include cellulose polymers,polyacrylic polymers, polyurethanes polymers, gelatins and gums.Specific examples include hydroxymethylcellulose, hydroxyethylcellulose,hydroxypropylcellulose, cellulose acetates, polyvinylidene andcopolymers of polyacrylic acid and polyacrylates.

Whilst the foregoing discussion relates to the temperature adjustingmeans being located within the wipe, the temperature adjusting means maybe located within the packaging in which the wipe is provided. Any ofthe arrangements detailed herein may be incorporated within thepackaging. In use, the user will activate the chemical adjusting meanswhile the wipe is within the packaging, allow the wipe to reach therequired temperature and then remove the wipe from the packaging foruse. In this arrangement, the wipe will generally be formed from acloth-type material.

In a preferred arrangement, the eyelid wipe will additionally beimpregnated with cleansing agents, surfactant agents or cleansing andsurfactant agents. The surfactants may be effective as cleaning agentsand/or solubilising agents. Any suitable cleansing or surfactant agentsmay be used and examples include PEG-80 sorbitan laurate, sodiumtrideceth sulfate, PEG-150 distearate, cocamidopropyl hydroxysultaine,sodium laureth-13 carboxylate, disodium lauroamphodiacetate, polysorbate80, polysorbate 20, poloxamer 184, ammonium laureth sulfate, ceteareth20,25, cocamidopropyl betaine, disodium laureth sulfosuccinate, disodiumlauriminodipropionate, disodium lauroamphodipropionate, glycol stearate,hydrogenated castor oil, laureth-23, magnesium laureth, oleth sulfate,PEG-20 stearate, PEG-35 castor oil, PEG-40 hydrogenated castor oil,PEG-60 hydrogenated castor oil, PEG-7 hydrogenated castor oil, PEG-75lanolin, poloxamers, sodium laureth sulfate, sodium trideceth sulfate,sodium C12-15 pareth 15 sulfonate, and sodium C14-16 olefin sulfonate.

Thus the invention in preferred embodiments provides for the controlleddelivery of an appropriate temperature with controlled delivery ofagents such as cleaning agents, surfactant agents or soothing agents.

The wipe may also include one or more of antistatic agents,preservatives, antioxidants, antimicrobial agents, chelating agents,emollients, emulsifying agents, buffering/neutralising agents,humectants, thickeners/viscosity controlling agents andantistatic/conditioning agents.

One example of a suitable preservative is imidazolidinyl urea. Suitableantioxidants include tocopherol and tocopheryl acetate. Suitableantimicrobial agents include quaternium-15. EDTA is one example of asuitable chelating agent. Sodium methylparaben, sodium propylparabem andquaternium 8,14 may also be present.

Examples of emollients include natural or mineral oils or esters.Specific examples include potassium C12-13 monoalkyl phosphatepolysorbate 60, potassium C12-13 monoalkyl phosphate, calendulaofficinalis, almond oil PEG-6 esters, capric/caprylic triglyceride,cetearyl alcohol, cocoa butter, decyl oleate, dimethicone, dimethiconecopolyol, glyceryl stearate, glyceryl caprylate, glyceryl oleate, glycolstearate, glycol oleate, hydrogenated castor oil, hydrogenated soybeanoil, laneth-10 acetate, lanolin, lanolin alcohol, acetylated lanolinalcohol, lecithin, PEG-11 castor oil, PEG-75 lanolin, petrolatum, PPG-26oleate, PEG-10 butanediol or stearyl alcohol.

Examples of emulsifying agents include PEG-6 caprylic/capric glyceride,ceteareth 20,25, cetearyl alcohol, glycereth-20 stearate, glycerylstearate, glyceryl caprylate, glyceryl oleate, glycol stearate, glycololeate, hydrogenated castor oil, laneth-10, laneth 10 acetate, lanolin,lanolin alcohol, laureth-23, lecithin, PEG-20 stearate, PEG-150distearate, PEG-40 hydrogenated castor oil, PEG 60 hydrogenated castoroil, PEG 7 hydrogenated castor oil, PEG-11 castor oil, PEG-35 castoroil, PEG-15 tallow polyamine, PEG-75 lanolin, poloxamer, polysorbate20,80, sodium laureth-13 carboxylate, sodium trideceth sulfate andstearic acid.

Examples of buffering/neutralising agents include dipotassium phosphate,sodium hydroxide, potassium phosphate, disodium phosphate, citric acid,aminomethyl propanediol, sodium hydroxide, diethanolamine bisulfate,ethanolamine, hydrochloric acid, lactic acid, sodium phosphate andtriethanolamine.

Examples of humectants include propylene glycol, glycereth-20, glycerin,hyaluronic acid, inositol, lactic acid, methyl gluceth-20, PEG-8, PEG-20stearate, sodium PCA and sorbitol.

Examples of thickeners/viscosity controlling agents such as carbomers,caprylic alcohol, cetearyl alcohol, dextran, disodiumlauroamphodiacetate, guar gum hydrogenated castor oil, laneth-10,magnesium sulfate, PEG-150 distearate, stearyl alcohol and xanthan gum.

Examples of antistatic/conditioning agents include dimethicone copolyol,disodium lauriminodipropionate, disodium lauroamphodiacetate, disodiumlauroamphodipropionate, glycol oleate, hyaluronic acid, inositol,lanolin, lanolin alcohol, lecithin, panthenol, PEG 15 tallow polyamine,petrolatum, polyquaternium 7,11,16,44 and sodium PCA.

The wipes may additionally or alternatively be impregnated with one ormore of the commercially available cleansing agents including those soldunder the trade names “Lid-Care” available from CibaVision, “Eye-Scrub”available from Novartis Opthalmics, “Lid Scrub”, “Igiene Daily EyelidCleanser” available from Igenics, “Blephasol” available from LaboratoireThea and “Supranettes” available from Alcon.

Additionally or alternatively, the eyelid wipe may be impregnated withactive agents such as anti-inflammatory and anti-bacterial agents and/ordecongestants. The use of the combination of heating, optionally alsowith cleaning, at the time that the active agents are applied to theeyelid, is believed to improve the efficacy of the active agents. Itwill therefore be understood that in this embodiment, the inventionprovides the controlled delivery of an appropriate temperature withcontrolled delivery of the appropriate amount of active agent,optionally with controlled delivery of the required amounts of cleansingsolution.

In one arrangement, one or more of cleansing agents, pharmaceuticalcompositions, active agents and the like may be located in a layer onthe outer surface of the wipe which is formed from a thermo-responsivepolymer which on heating would soften so that the polymer matrix willreduce the active agent.

In one preferred arrangement, the temperature adjusting means providecooling and one or more active agents such as anti-inflammatory agents,anti-bacterial agents and/or decongestants are present. Such wipes areparticularly useful in the treatment of the symptoms of, for example,hayfever.

The wipe may include, or may be combined with, a drug delivery systemsuch that there is achieved a system which enables the controlleddelivery of an appropriate temperature in combination with controlleddelivery of a pharmaceutical.

It will be understood that care will be taken in the selection of heatadjusting means and any other components present to ensure thatcomponents and products of reaction are not liable to cause damage tothe delicate eye region. Where a selection is made where direct contactwith the eye region is not advisable, the materials will generally beenclosed within a container in the wipe.

Where the wipe is multi-layered, or where the wipe includes a containerfor one or more of the components of the chemical heat adjusting means,the edges of the wipe may be sealed either directly or via anintermediate sealing means. Any suitable means of sealing may be used.Suitable means include the use of adhesive, including hot melt andpressure sensitive adhesive, double sided adhesive tape, heat sealing orultrasonic bonding. In general, the sealing means will be selected suchthat there is no hard residue which would be uncomfortable when the wipeis in use.

The present invention also provides the use of the wipe of theabove-mentioned first aspect in the treatment of disorders of the eyelidor eyelid margin. In a preferred arrangement of this second aspect ofthe present invention, there is provided the use of the wipe of theabove-mentioned first aspect in the treatment of meibomian glanddisorder. In an alternative arrangement of this second aspect of thepresent invention, there is provided the use of the wipe of theabove-mentioned first aspect in the treatment of inflammation of theeyelid. In this arrangement, the temperature adjustment of the wipe ispreferably cooling.

In a further aspect of the present invention, the application alsoprovides a method of treating meibomian gland dysfunction and/orblepharitis comprising allowing the wipe of the above first aspect toreach temperature and then massaging the eyelid margin with the wipe.Cleansing agents or the like may be applied to the wipe before massagingis commenced.

In use, it may be desirable for the user to leave the wipe against theeye for a short period prior to commencing massaging of the eyelidmargin with the wipe. The period of time required may be of the order ofabout 5 minutes to about 10 minutes.

BRIEF DESCRIPTION OF THE DRAWINGS

The wipe of the present invention will now be described by way ofexample, with reference to the accompanying drawings in which:

FIG. 1 illustrates a circular wipe with heat delivery system;

FIG. 2 illustrates a tubular wipe with heat delivery system;

FIG. 3 illustrates an alternative tubular wipe with heat deliverysystem;

FIG. 3 a illustrates the sides of the tubular wipe of FIG. 3;

FIG. 3 b illustrates a modification to the tubular wipe of FIG. 3;

FIG. 4 a illustrates an ovoid shaped wipe with an alternative heatdelivery system;

FIG. 4 b illustrates an alternative arrangement for the ovoid shapedwipe;

FIG. 5 illustrates a folded cloth-like wipe;

FIG. 6 is a graph representing the results of the Comparative Example 2;

FIG. 7 is a graph representing the temperature changes noted for theformulation of Example 1;

FIG. 8 is a graph representing the temperature changes noted for theformulation of Example 2;

FIG. 9 is a graph representing the temperature changes noted for theformulation of Example 3;

FIG. 10 is a graph representing the temperature changes noted for theformulation of Example 4;

FIG. 11 is a graph representing the temperature changes noted for theformulation of Example 5;

FIG. 12 is a graph representing the temperature changes noted for theformulation of Example 6;

FIG. 13 is a graph representing the temperature changes noted for theformulation of Example 7;

FIG. 14 is a graph representing the temperature changes noted for theformulations of Examples 8 to 10;

FIG. 15 is a graph representing the temperature changes noted for theformulations of Examples 11 to 13;

FIG. 16 is a graph representing the temperature changes noted for theformulations of Examples 14 to 17;

FIG. 17 is a graph representing the temperature changes noted for theformulations of Examples 18 to 20;

FIG. 18 is a graph representing the temperature changes noted for theformulations of Examples 21 to 30;

FIG. 19 is a graph representing the temperature changes noted for theformulations of Examples 31 to 34;

FIG. 20 is a schematic representation of the wipe of Example 35;

FIG. 21 is a further schematic representation of the wipe of Example 35at activation;

FIG. 22 is a picture of the water bubbles used in Example 35;

FIG. 23 is a picture of part of a prototype wipe of Example 35;

FIG. 24 is a graph of the temperature profile achieved for the wipe ofExample 35;

FIG. 25 is a graph representing the temperature changes noted for theformulations of Examples 36 to 46;

FIG. 26 is a graph representing the temperature changes noted for theformulations of Examples 47 to 49;

FIG. 27 is a picture of uncoated cooling prototype;

FIG. 28 is a graph representing the temperature changes noted for theformulations of Example 50;

FIG. 29 is a schematic representation of the wipe of Example 51;

FIG. 30 is a further schematic representation of the wipe of Example 51at activation;

FIG. 31 is a picture of an alternative cooling prototype;

FIG. 32 is a graph representing the temperature changes noted for theformulations of Example 51; and

FIG. 33 is a graph representing the temperature changes noted for thefinger shaped arrangement of Example 52.

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENT

In one embodiment of the present invention as described in FIG. 1, thewipe 1 is of circular configuration and is formed from a layeredstructure. The layers present comprise a porous outer layer 2, a layer 3impregnated with cleaning agent, a heat generating layer 4 comprisingmaterial which on exposure to air or water generates heat. This layer isoptionally backed by a heat reflective layer 5 which serves to directthe heat released by the heat generating layer 4 towards the outer layer2. These layers are supported on a holding layer 6 which is generallycloth-like and will form the outer layer which the user will hold intheir hand. The wipe 1 will generally be sealed around the edge. Theedge margin may comprise solely the porous outer layer 2 and the holdinglayer 6 bonded together.

As illustrated in FIG. 2, the wipe 1A may be provided as a tube intowhich the user may insert a finger to facilitate the massaging steprequired in use. Here the wipe 1A is formed in a similar manner to thecircular wipe of FIG. 1. It will generally be formed as a rectangularmaterial comprising a porous outer layer 2, a layer impregnated withcleaning agent 3, a heat generating layer 4, a heat reflective layer 5and a holding layer 6. When this rectangle is formed into a tube, theholding layer 6 becomes the inner wall of the tube. In this arrangement,the inner wall may be cloth-like or sponge-like.

A modification of the tubular wipe is a wipe having a closed end so thatthe user's finger does not protrude through the wipe. The wipe 1B mayhave the same configuration throughout the sides of the wipe such as inthe tubular arrangement of FIG. 2 as illustrated in FIG. 3B or in thealternative arrangement illustrated in FIG. 3A the wipe may have a sideA′ which will, in use, be placed against the eye. The user wouldnormally have this side located on the inside of their finger. The wipeof FIG. 3B will also have a plain holding layer B′ for the exterior ofthe finger. In this arrangement the side A′ of the finger wipe will havea similar structure to that of the circular wipe of FIG. 1.

An alternative arrangement is illustrated in FIG. 4 a. In thisarrangement, the wipe 1C has an ovoid configuration to mirror theoverall eye shape. In the centre of the ovoid is a pressure point 7which when pressed activates the chemical reaction. In this wipe, atwo-component means is used to cause the adjustment of temperature. Thewipe contains an inner breakable pouch 8 which in A contains seedcrystals and in B a metallic trigger. When the user depresses the wipeat the pressure point 7, the pouch breaks such that the seedcrystals/metallic trigger come into contact with an aqueous saltsolution in which the wipe is first soaked. The wipe of FIG. 4additionally comprises an optional self-adhesive layer 9. As illustratedin FIG. 4 b the pressure point 7 may be located to one side of the wipe.

In FIG. 5, the wipe 1D, which on this occasion is a folded cloth-likewipe impregnated with substances which will generate heat when treatedwith an aqueous solution. Cleaning agents are also impregnated into thewipe. The folded wipe is provided in a moisture impermeable pouch 10.

The invention will now be described with reference to the followingexamples.

Comparative Example 1 Determination of Target Temperature for a Hot Wipein Particular for Use in the Treatment of Meibomian Gland Dysfunction

A cloth was immersed in boiling water and then removed. The temperatureof the cloth was measured and the skin tolerance to the cloth wasevaluated. The skin tolerance was evaluated by placing the cloth on theinside of the wrist. It was found that the temperature reached was muchhigher than was acceptable in terms of skin tolerance and that thereforeif such a cloth were to be used as a hot compress in the treatment of,for example, meibomian gland dysfunction, there was a risk that injurycould occur to the patient. The tolerance level was found to be in theregion of 53° C. Temperatures of 43° C. and below were said by thesubjects to be not hot enough for any beneficial effect to be felt. Theresults are summarised in Table 1

TABLE 1 WARM CLOTH Temperature Out of boiling water approx 63° C. Maxtolerable to skin approx 52-53° C. “Not hot enough” (skin) approx 43° C.

Comparative Example 2

Comparative Example 1 was repeated using a cloth impregnated with heatedsaline solution. The compress was applied to a closed eye to mimic theroutine used by a patient following the conventional treatment formeibomian gland dysfunction. The average results for 10 subjects aresummarised in Table 2 below and in the graph of FIG. 6.

TABLE 2 WARM CLOTH Temperature “Too hot” approx >54° C. “Bearable” (eyearea) approx 53° C. “Comfortable” (eye area) approx 51° C.

Thus it was noted that a temperature of above 54° C. was uncomfortable.It was often expressed as being too hot for the subjects. The optimaltemperature was found to be in the region of 51° C. Thus a temperaturerange of from about 45° C. to about 52° C. is preferred. For maximumefficacy the temperature should be sustained for 10 minutes.

Various formulations for the chemical temperature adjusting means wereinvestigated.

Example 1 Air Triggered System

A sealed pouch was prepared into which a powder comprising 59% ironpowder, 21% water, 10.5% vermiculite, 4% activated charcoal and 5% salthad been placed. The pouch was opened and the temperature changes werenoted. These are represented graphically in FIG. 7.

Example 2 Water Triggered System A

A sealed pouch was prepared into which anhydrous sodium carbonate hadbeen placed. Water was added to the pouch and the temperature changeswere noted. These are represented graphically in FIG. 8.

Example 3 Water Triggered System B

A sealed pouch was prepared into which anhydrous magnesium sulphate hadbeen placed. Water was added to the pouch and the temperature changeswere noted. These are represented graphically in FIG. 9.

Example 4 Water Triggered System C

A sealed pouch was prepared into which anhydrous magnesium sulphate (25%w/w) and propylene glycol (75% w/w) or PEG400 (75% w/w) had been placed.Water was added to the pouch and the temperature changes were noted.These are represented graphically in FIG. 10.

Example 5 Water Triggered System D

A sealed pouch was prepared into which anhydrous sodium potassiumaluminosilicate 3 Å (35% w/w), PEG200 (55% w/w) and glycerin (10% w/w)had been placed. Water was added to the pouch and the temperaturechanges were noted. These are represented graphically in FIG. 11.

Example 6 Two Component System A

A two component system was prepared. The first component comprised thereducing agent thiourea and the second comprised the oxidation agenthydrogen peroxide solution (approx 8%). The two components were mixedand the temperature changes were measured. These are representedgraphically in FIG. 12.

Example 7 Two Component System B Utilising a Supersaturated SaltSolution

10 g anhydrous sodium acetate were mixed with 7.5 g water. After theaddition of a few salt seed crystals, the temperature changes weremeasured and are represented in FIG. 13.

Examples 8 to 30 Optimisation Of Temperature Profile

In order to optimise the temperature profile for an inorganic salt/watersystem various compositions as detailed in Table 3 were investigated.The temperature changes measured are represented graphically in FIGS. 14to 19.

TABLE 3 Example Formulation FIG. 8 2.5 g MgSO₄/7.5 g PEG 400: 40 ml H₂O14 9 2.5 g MgSO₄/7.5 g PEG 400: 20 ml H₂O 14 10 2.5 g MgSO₄/7.5 g PEG400: 10 ml H₂O 14 11 2.5 g MgSO₄: 10 ml H₂O 15 12 2.5 g MgSO₄/7.5 gglyerol: 10 ml H₂O 15 13 2.5 g MgSO₄/7.5 g PEG 400: 10 ml H₂O 15 14 5 gMgSO₄/5 g PEG 400: 10 ml H₂O 16 15 5 g MgSO₄/10 g PEG 400: 10 ml H₂O 1616 5 g MgSO₄/15 g PEG 400: 10 ml H₂O 16 17 5 g MgSO₄/10 g PEG 400/5 gglycerol: 10 ml H₂O 16 18 4 g MgSO₄/8 g PEG 400/4 g glycerol: 10 ml H₂O17 19 4 g MgSO₄/12 g PEG 400: 10 ml H₂O 17 20 3 g MgSO₄/9 g PEG 400: 10ml H₂O 17 21 2.5 g MgSO₄: 10 ml H₂O 18 22 2.5 g MgSO₄/7.5 g glycerol: 10ml H₂O 18 23 2.5 g MgSO₄/7.5 g PEG 400: 10 ml H₂O 18 24 5 g MgSO₄/5 gPEG 400: 10 ml H₂O 18 25 5 g MgSO₄/10 g PEG 400: 10 ml H₂O 18 26 5 gMgSO₄/15 g PEG 400: 10 ml H₂O 18 27 5 g MgSO₄/10 g PEG 400/5 g glycerol:10 ml H₂O 18 28 4 g MgSO₄/8 g PEG 400/4 g glycerol: 10 ml H₂O 18 29 4 gMgSO₄/12 g PEG 400: 10 ml H₂O 18 30 3 g MgSO₄/9 g PEG 400: 10 ml H₂O 18

For the formulations of Examples 23 and 30 the heat generated was bettersustained between 7 and 10 minutes post activation and therefore offeredadvantages when compared with the other formulations.

Examples 31 to 34

Further tests were carried out to optimise the salt mixture system withMgSO4 from 2.5 g to 4 g. The details are set out in Table 4 and thetemperature profile are represented graphically in FIG. 19.

TABLE 4 Example Formulation FIG. 31 2.5 g MgSO₄/7.5 g PEG 400: 10 ml H₂O19 32 3 g MgSO₄/9 g PEG 400: 10 ml H₂O 19 33 3.5 g MgSO₄/10.5 g PEG 400:10 ml H₂O 19 34 4 g MgSO₄/12 g PEG 400: 10 ml H₂O 19

The formulation of Example 33 sustained a temperature of just below 45°C. after 7 minutes and was therefore chosen for use in Example 35 in theproduction of a prototype wipe.

Example 35 Prototype Heating Wipe

A prototype was produced based on a water triggered system which wasactivated by pressure. The heat produced was the result of theexothermic reaction of the inorganic salt mixture with water. The waterwas provided as a water bubble within a frangible plastic envelope ofpolyethylene as illustrated in FIG. 22. Two water bubbles were used eachcontaining 5 ml water. The water bubbles and the salt mixture of 3.5 gMgSO₄/10.5 g PEG 400 were inserted in a sealable water-tight pouch toform the heat-generating compartment 11 of FIG. 20. The heat generatingcompartment 11 is coated on one side 12 with a sheet of aluminium foilcovered with gauze and on the other side 13 with a cotton pad. In use itis the side 12 which is applied to the closed eyelids for the heattreatment. After heat treatment side 13 can be impregnated with cleaningsolution and used to wipe the lid margin. The pad on side 13 may, in analternative arrangement, be pre-impregnated with the cleaning solution.A picture of the prototype wipe is in FIG. 23. In production the wipewill generally be of an optimum size and shape for use by the user.

The operation of wipe is illustrated schematically in FIG. 21. Gentlepressure on the external surfaces of the wipe causes the water bubbles14 to burst so that the water comes into contact with the inorganic saltmixture 15 so that heat is released. The temperature profile isillustrated graphically in FIG. 24. As indicated above, a temperature offrom 45 to 52° C. is desirable. The wipe reached the requiredtemperature within 1 minute of activation and the temperature wasmaintained for 10 minutes. Crystallisation occurred.

Example 36 to 46 Water Triggered System for Cooling

Various compositions were prepared as detailed in Table 5 and thetemperature profiles on the addition of water were measured. The resultsare illustrated graphically in FIG. 25.

TABLE 5 Example Formulation FIG. 36 5 g NH₄NO₃: 10 ml H₂O 25 37 7.5 gNH₄NO₃: 10 ml H₂O 25 38 10 g NH₄NO₃: 10 ml H₂O 25 39 7.5 g NH₄NO₃/7.5 mlglycerol: 10 ml H₂O 25 40 7.5 g NH₄NO₃/7.5 ml PEG400: 10 ml H₂O 25 41 10g NH₄NO₃/5 ml glycerol: 10 ml H₂O 25 42 10 g NH₄NO₃/1 g Carbopol 25ETD2020: 10 ml H₂O 43 10 g NH₄NO₃/0.75 g Carbopol 25 ETD2020: 10 ml H₂O44 10 g NH₄NO₃/0.5 g Carbopol 25 ETD2020: 10 ml H₂O 45 15 g NH₄NO₃/0.75g Carbopol 25 ETD2020: 10 ml H₂O 46 12.5 g NH₄NO₃/0.75 g Carbopol 25ETD2020: 10 ml H₂O 47 10 g NHNO₃/0.75 g Carbopol 26 ETD2020: 10 ml H₂O48 12.5 g NH₄NO₃/0.75 g Carbopol 26 ETD2020: 10 ml H₂O 49 15 gNH₄NO₃/0.75 g Carbopol 26 ETD2020: 10 ml H₂O

Example 50 Prototype Cooling Wipe

A prototype was produced based on a water triggered system which wasactivated by pressure. The cold produced was the result of theendothermic reaction of the ammonium nitrate with water. The water wasprovided as a water bubble within a frangible plastic envelope ofpolyethylene as illustrated in FIG. 22. One water bubble was usedcontaining 10 ml water. The water bubble and the salt mixture of 10 g to15 g NH₄NO₃/0.75 g ETD2020 (as detailed in Table 6) were inserted in asealable water-tight pouch to form the cold-generating compartment 21 ofFIG. 29. In this example, the cold generating compartment 21 was leftuncoated. Pressure was applied to the water bubble such that the watermixed with the ammonium nitrate and cold was generated. The temperatureprofiles are illustrated graphically in FIG. 28.

TABLE 6 Run Formulation FIG. A 10 g NH₄NO₃/0.75 g ETD2020: 10 ml H₂O 28B 12.5 g NH₄NO₃/0.75 g ETD2020: 10 ml H₂O 28 C 15 g NH₄NO₃/0.75 gETD2020: 10 ml H₂O 28

Example 51 Prototype Cooling Wipe 2

Example 51 was repeated except that the wipe was left uncoated on oneside 22 and was coated on the other side 23 with a cotton pad. In use itis the side 22 which is to be applied to the closed eyelids for thecooling treatment. After cooling treatment side 23 can be impregnatedwith any applicable treatment solution and used to wipe the lid margin.The pad on side 23 may be pre-impregnated with the cleaning solution. Apicture of the prototype wipe is in FIG. 31. In production the wipe willgenerally be of an optimum size and shape for use by the user.

The operation of the wipe is illustrated schematically in FIG. 30.Gentle pressure on the external surfaces of the wipe causes the waterbubble 24 to burst so that the water comes into contact with theinorganic salt mixture 25 so that cooling is released. The temperatureprofile is illustrated graphically in FIG. 32.

Example 52 Prototype Finger Shaped Heating Wipe

Example 35 was repeated except that the water bubbles and the saltmixture in the sealable water-tight pouch were placed in the thumb of aglove. The temperature profile achieved is illustrated graphically inFIG. 33.

Example 53 Alternative Prototype

Two plastics sheets comprising three layers, an outer layer ofpolypropylene, an amorphous intermediate metallic oxide layer and aninner layer of polyethylene, are thermo-sealed around three sides toform a pouch. The pouch is then further sealed with a rupturable seal inthe middle to create two chambers. A salt/PEG mixture is placed in onechamber and water into the other. The mouth of the pouch is thenthermo-sealed. One external face of the pouch is coated with apolystyrene insulating layer and gauze is applied to the other facewhich when the wipe is in use will be in contact with the eyelid margin.

What is claimed is: 1-40. (canceled)
 41. An eyelid wipe for treatment ofa disorder of an eye, eyelid, or eyelid margin, comprising: a) at leasttwo components adapted to lower a temperature of the eyelid wipe from anambient temperature to a desired temperature upon a reaction of the atleast two components, b) a water-impermeable container for preventingthe at least two components from coming into contact with a closed eyewhen in use, c) a seal for keeping the at least two components separateuntil a temperature change is initiated, and d) at least one agentselected from the group consisting of soothing agents, cleansing agents,and surfactant agents.
 42. The eyelid wipe of claim 41, wherein thedisorder is blepharitis, dryness, irritation, redness, inflammation,meibomian gland dysfunction, hay fever, a condition associated with useof eye cosmetics, or a condition associated with contact-lens wear. 43.The eyelid wipe of claim 41, wherein the reaction is an endothermicreaction.
 44. The eyelid wipe of claim 41, wherein one of the at leasttwo components is a hydratable inorganic salt.
 45. The eyelid wipe ofclaim 41, wherein one of the at least two components is NH₄NO₃.
 46. Theeyelid wipe of claim 41, wherein the at least two components compriseNH₄NO₃ and water.
 47. The eyelid wipe of claim 41, wherein the at leasttwo components comprise an oxidising agent and a reducing agent.
 48. Theeyelid wipe of claim 41, wherein the desired temperature is from about0° C. to about 25° C.
 49. The eyelid wipe of claim 41, wherein thedesired temperature is from about 5° C. to about 10° C.
 50. The eyelidwipe of claim 41, wherein the desired temperature is reached within 2minutes after the temperature change is initiated.
 51. The eyelid wipeof claim 41, wherein the desired temperature is reached within 1 minuteafter the temperature change is initiated.
 52. The eyelid wipe of claim41, wherein the desired temperature is reached in less than about 60seconds after the temperature change is initiated.
 53. The eyelid wipeof claim 41, wherein the desired temperature is reached in from about 30to about 60 seconds after the temperature change is initiated.
 54. Theeyelid wipe of claim 41, wherein the desired temperature is maintainedfor at least about 5 minutes.
 55. The eyelid wipe of claim 41, whereinthe desired temperature is maintained for at least about 8 minutes. 56.The eyelid wipe of claim 41, wherein the desired temperature ismaintained for at least about 10 minutes.
 57. The eyelid wipe of claim41, wherein the desired temperature is maintained for from about 5minutes to about 30 minutes.
 58. The eyelid wipe of claim 41, whereinthe eyelid wipe is sterile.
 59. The eyelid wipe of claim 41, wherein theeyelid wipe is square, rectangular, circular, ovoid, eye-shaped, curvedto correspond to a contour of an eye, sized to be used on one eyeregion, or sized to be used on two eyes simultaneously.
 60. The eyelidwipe of claim 41, further comprising a band, a pocket, or a layer forholding the eyelid wipe for a period of time.
 61. The eyelid wipe ofclaim 60, comprising the band that is elastic.
 62. The eyelid wipe ofclaim 41, further comprising an adhesive portion on a part or the wholeof one side of the eyelid wipe.
 63. The eyelid wipe of claim 62, whereinthe adhesive portion comprises one or more adhesive materials selectedfrom the group consisting of acrylic adhesives, hydrocolloidal orhydrogel adhesives, natural rubber, synthetic rubber, and anycombination thereof.
 64. The eyelid wipe of claim 41, further comprisinga removal strip to protect an adhesive portion.
 65. The eyelid wipe ofclaim 64, wherein the removal strip is a polymer or paper strip treatedwith silicone.
 66. The eyelid wipe of claim 41, wherein the eyelid wipeis coated with a polymeric material capable of moulding to a surface ofan eye.
 67. The eyelid wipe of claim 41, wherein the seal is a frangibleseal.
 68. The eyelid wipe of claim 41, wherein the at least one agent isat least one cleansing agent or at least one surfactant agent.
 69. Theeyelid wipe of claim 41, wherein the at least one agent is PEG-80sorbitan laurate, sodium trideceth sulfate, PEG-150 distearate,cocamidopropyl hydroxysultaine, sodium laureth-13 carboxylate, disodiumlauroamphodiacetate, polysorbate 80, polysorbate 20, poloxamer 184,ammonium laureth sulfate, ceteareth 20, ceteareth 25, cocamidopropylbetaine, disodium laureth sulfosuccinate, disodiumlauriminodipropionate, disodium lauroamphodipropionate, glycol stearate,hydrogenated castor oil, laureth-23, magnesium laureth, oleth sulfate,PEG-20 stearate, PEG-35 castor oil, PEG-40 hydrogenated castor oil,PEG-60 hydrogenated castor oil, PEG-7 hydrogenated castor oil, PEG-75lanolin, poloxamer, sodium laureth sulfate, sodium trideceth sulfate,sodium C12-15 pareth 15 sulfonate, sodium C14-16 olefin sulfonate, orany combination thereof.
 70. The eyelid wipe of claim 41, furthercomprising a drug delivery system.
 71. The eyelid wipe of claim 41,further comprising at least one additional agent selected from the groupconsisting of anti-inflammatory agents, anti-bacterial agents,decongestants, antistatic agents, preservatives, antioxidants,antimicrobial agents, chelating agents, emollients, emulsifying agents,buffering/neutralising agents, humectants, thickeners, viscositycontrolling agents, antistatic agents, conditioning agents, and anycombination thereof.
 72. The eyelid wipe of claim 71, comprising theviscosity controlling agent that is polyethylene glycol (PEG).
 73. Theeyelid wipe of claim 41, further comprising a reflective layer or aconductive layer to direct cooling towards a surface of the eyelid wipe.74. The eyelid wipe of claim 41, further comprising an indicator whichconfirms to a user that the desired temperature is reached.
 75. Theeyelid wipe of claim 74, wherein the indicator is a temperaturesensitive color indicator configured to change from a first color to asecond color when the desired temperature is reached.
 76. The eyelidwipe of claim 75, wherein the indicator is configured to undergo areversible color change, such that when the eyelid wipe is no longer atthe desired temperature or falls outside of a desired temperature range,the indicator reverts to the first color.
 77. The eyelid wipe of claim74, wherein at least a part of the eyelid wipe is coated with atemperature reactive ink or a temperature reactive dye.